Abstract: Age-related macular degeneration
(AMD) is a major cause of blindness in older people and is caused by loss of
the central region of the retinal pigment epithelium (RPE). Conventional
methods of gene expression analysis have yielded important insights into AMD
pathogenesis, but the precise molecular pathway alterations are still poorly
understood. Therefore we developed a new software program, "AMD
Medicine", and discovered differential pathway activation profiles in
samples of human RPE/choroid from AMD patients and controls. We identified 29
pathways in RPE-choroid AMD phenotypes: 27 pathways were activated in AMD compared
to controls, and 2 pathways were activated in controls compared to AMD. In AMD,
we identified a graded activation of pathways related to wound response,
complement cascade, and cell survival. Also, there was downregulation of two
pathways responsible for apoptosis. Furthermore, significant activation of
pro-mitotic pathways is consistent with dedifferentiation and cell
proliferation events, which occur early in the pathogenesis of AMD.
Significantly, we discovered new global pathway activation signatures of AMD involved
in the cell-based inflammatory response: IL-2, STAT3, and ERK. The ultimate aim
of our research is to achieve a better understanding of signaling pathways
involved in AMD pathology, which will eventually lead to better treatments.